The transformation of an organism is a generic term for multiple techniques including the introduction of a foreign gene into the genome of organism by artificial means and expression of the same; the induction and manipulation of overexpression of intrinsic gene; the knockout of a specific gene on the genome to identify the phenotypic changes induced by the gene expression and the function of the genes, for improving animals and plants, increasing productivity, and for generating useful industrial medical products.
The introduction of a foreign gene into an organism can be done by various methods such as, for the transformant animal, the microinjection to a fertilized egg by microinjector, use of viruses in various forms, use of electromagnetic field, and use of chemicals such as lipids, depending on the purpose. Also, the expression of a target gene can be limited to a specific tissue by using a promoter that can induce the expression of a foreign gene, or can be induced according to the developmental stage of an organism.
Methods of transformation for application to animals have been developed and could be commercialized according to many studies. In particular, transformed and cloned animals have been used for the improvement of livestock and development of new variety, enhancement of disease endurance to the diseases that occur frequently in livestock, improvement of the quality of by-product that can be obtained from livestock, production of disease-model animal, development of organ donor animal that can substitute the organ injury caused by human diseases or natural disasters, and production of useful substance using a bioreactor system.
Cloning refers to the generation of a genetically identical subject. Nuclear transfer is one of the cloning methods for eukaryotes and it grabs new attention due to recent developments in molecular biology field. Early nuclear transfer technique used a blastomere of fertilized egg as nuclear donor (Prather et al., Biol. Reprod., 1987, 37:856-866; Prather et al., Biol. Reprod., 1989, 41:414-418), but recently a nucleus of somatic cell is used instead.
Somatic cell cloning is a technique for creating a fertilized egg by inserting a differentiated somatic cell to enucleated oocyte and activating the same. Said cloning technique not only can be widely used in the researches in basic science field including developmental biology, but is also expected to provide large contribution to various medical and pharmacological fields such as production of useful proteins, development of disease-model, and organ transfer, thereby demonstrating a large industrial usefulness. That is, a production system using said technique is highly cost-effective, and thus it can produce a bioactive substance at lower cost, which is currently sold at a high price. Furthermore, said production system utilizes the animal that is physiologically closest to a human body as a system for producing physiologically active substance, and thus high quality product can be produced. Also, since the in vivo protein production system of animal is used, a large-scale production is possible, and particularly for drug development such as vaccine for ingestion, no separate purification process is needed.
Meanwhile, as for organ transplantation, which transplants a portion of or whole organ to a recipient who lost a functional organ and thus cannot receive any more treatment such as drug treatment, those organs are mostly taken from live persons. However, the number of donors is significantly lower than the number of waiting recipients. Thus, there have been many attempts to solve these problems. For instance, stem cell transplantation and transplantation of xenogeneic organ have been developed. The stem cell transplantation can be used to substitute damaged cells by proliferating the cells as many as required, but these cells cannot be developed into an organ, which is composed of various types of cells. Thus, if organ transplantation is needed, xenograft may be used to directly replace the damaged organ. Heteroplastic transplantation using animals, which can provide sufficient number of donor organs, has been emerged as one of various methods that can substitute human organ. However, when a xenogeneic organ is transplanted to human body, severe multiphasic immune responses and inflammatory responses are induced. In particular, pigs have very similar anatomical and physiological structure as humans, and the organ size thereof is similar to that of humans. Also, transplantation of pig organ has advantages of easy breeding, short pregnancy period (112 days), and bearing a large number of piglings at once (6 to 12). However, when the pig organ is transplanted in human body, severe multiphasic immune responses and inflammatory responses will be induced. Therefore, resolving the problem of immune response and inflammatory response is a remaining task to be solved for conducting heteroplastic transplantation.